Optimal interpretation of pleasurable, rewarding experiences favors decisions that enhance survival. However, pleasure seeking can also lead to deleterious and life- threatening behaviors, exemplified by abusive drug addiction, impulsive thrill seeking and adverse risk taking. These reward mechanisms are supported, in part, by activity in dopamine pathways of the brain, including the ventral tegmental nuclei and striatum. One circumstance increasingly related to altered dopaminergic brain reward sensitivity is the state of sleep deprivation. Sleep loss can trigger amplified reactivity in dopaminergic networks in response to pleasurable experiences, elevate levels of dopamine within these circuits, and sensitivity to dopamine throughout these networks. Despite such emerging evidence, the impact of sleep loss on human brain reward processing and associated behaviors remains largely uncharacterized. Furthermore, the degree to which these neural and behavioral processes are supported by healthy sleep, is similarly unknown. The need to characterize this potentially causal interaction is worthy of attention considering the known disruption of sleep in numerous addiction disorders associated with altered reward brain activity. Identifying such an interaction would implicate sleep loss as a predisposing risk factor in heightened responsivity and hence addiction potential to reward- stimulating drugs. It would further indicate a role for sleep disruption in the maintenance of addiction habits, especially during attempted withdrawal. Using functional MRI scanning in combination with established reward paradigms and sleep physiological recordings, here we propose to test the central hypothesis that (i) sleep deprivation amplifies sensitivity of the human mesolimbic system in response to reward incentives, which additionally (ii) biases the brain towards disproportionately reward-driven hippocampal learning, and (iii) REM sleep quantity and spectral quality during normal sleep is predictive of these neural and behavioral reward processes. Therefore, this proposal represents a systematic evaluation of how sleep loss and sleep physiology causally amplify human brain reward sensitivity, altering associated behaviors, and whether such dysfunction is normally regulated by habitual sleep. Considering the high prevalence and comorbidity of sleep disruption in addiction disorders, the proposed research holds substantive and direct clinical as well as broad public-health ramifications, with logical next-step translational targets.